Biology subjects

Radecki, D. Z.

Publications and source records attributed to Radecki, D. Z..

3 recordsLinked to original sources

bioRxiv2023

Wobbly hedgehog syndrome- a progressive neurodegenerative disease

Wobbly hedgehog syndrome (WHS) has been long considered to be a myelin disease primarily affecting the four-toed hedgehog. In this study, we have shown for the first time that demyelination is accompanied by extensive remyelination in WHS. However, remyelination is not enough to compensate for the axonal degeneration and neuronal loss, resulting in a progressive neurodegenerative disease reminiscent of progressive forms of multiple sclerosis (MS) in humans. Thus, understanding the pathological features of WHS may shed light on the disease progression in progressive MS and ultimately help to develop therapeutic strategies for both diseases. HighlightsO_LIWobbly hedgehog syndrome (WHS) is a progressive neurodegenerative disease. C_LIO_LISpongy degeneration of the brain and spinal cord is the diagnostic feature of WHS. C_LIO_LIWHS affected brain and spinal cord show extensive demyelination and remyelination. C_LIO_LIAxonal degeneration is accompanied by loss of neurons in WHS. C_LI O_FIG O_LINKSMALLFIG WIDTH=185 HEIGHT=200 SRC="FIGDIR/small/547983v1_figu1.gif" ALT="Figure 1"> View larger version (50K): org.highwire.dtl.DTLVardef@cb6155org.highwire.dtl.DTLVardef@634d4dorg.highwire.dtl.DTLVardef@1681726org.highwire.dtl.DTLVardef@c80123_HPS_FORMAT_FIGEXP M_FIG Graphical Abstract C_FIG

neuroscience↗

bioRxiv2021

Gpnmb inhibits oligodendrocyte differentiation of adult neural stem cells by amplifying TGFβ1 signaling

Gli1 expressing neural stem cells, in the subventricular zone of the adult mammalian brain, respond to demyelination injury by differentiating into oligodendrocytes. We have identified Gpnmb as a novel regulator of oligodendrogenesis in Gli1 neural stem cells, whose expression is induced by TGF{beta}1 signaling via Gli1, in response to a demyelinating injury. Upregulation of Gpnmb further activates the TGF{beta}1 pathway by increasing the expression of the TGF{beta}1 binding receptor subunit, TGF{beta}R2. Thus the TGF{beta}1[->]Gli1[->]Gpnmb[->]TGF{beta}R2 signaling pathway forms a feed forward loop for sustained activation of TGF{beta}1 signaling in Gli1 neural stem cells, resulting in inhibition of their differentiation into mature oligodendrocytes following demyelination.

neuroscience↗

bioRxiv2019

Gli2 is necessary for migration of ventral Neural Stem Cells to demyelinated lesions

Enhancing repair of myelin is an important therapeutic goal in many neurological disorders characterized by demyelination. In the healthy adult brain, ventral neural stem cells in the sub-ventricular zone are marked by Gli1 expression and do not generate oligodendrocytes. However, in response to demyelination they migrate to lesions and differentiate into oligodendrocytes. Inhibition of Gli1 further increases their contribution to remyelination. Gli1 and Gli2 are both transcriptional effectors of the Sonic Hedgehog pathway with highly conserved domains but the role of Gli2 in remyelination by ventral neural stem cells is not clear. Here we show that while genetic ablation of Gli1 in the ventral neural stem cells increases remyelination, loss of Gli2 in these cells decreases their migration to the white matter lesion and reduces their differentiation into mature oligodendrocytes. These studies indicate Gli1 and Gli2 have distinct, non-redundant functions in NSCs, including that Gli2 is essential for the enhanced remyelination mediated by Gli1 inhibition. They highlight the importance of designing specific Gli1 inhibitors that do not inhibit Gli2 as a strategy for therapies targeting the Shh pathway.\n\nGraphical Abstract\n\nO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=157 SRC=\"FIGDIR/small/668418v1_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (36K):\norg.highwire.dtl.DTLVardef@177fa0aorg.highwire.dtl.DTLVardef@1c0a954org.highwire.dtl.DTLVardef@1accdc5org.highwire.dtl.DTLVardef@1f97eeb_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗